Project 4: Brain Activation Profiles of Reading Disabilities in Children: A Magnetic Source Imaging Study. Project 4 (MSI) proposes the use of magnetoencephalography, also known as magnetic source imaging (MSI), to evaluate the neural correlates of reading and reading intervention in children at risk for or with identified disabilities involving reading. This objective will be completed in relation to specific features of the brain activation profiles associated with different subtypes of poor readers based on the Reading Components model in Project 1 (Classification) and with adequate and inadequate response to different interventions in Projects 2 (Early Intervention) and 3 (Remediation). In a series of functional imaging studies using MSI, we have shown that (a) there exists a profile of brain activation recognizable at the single subject level, specific to a number of reading tasks;(b) children with dyslexia (defined as a word level reading disorder) produce a distinctly different activation profile when engaged in these same tasks, also recognizable at the single subject level;(c) that the profile is specific to dyslexia and not to the usual comorbidities (e.g. attention deficit hyperactivity disorder) and associated disorders (e.g., math difficulties); and (d) that the profile changes as a result of successful reading interventions. To build upon this research, we propose three specific aims in an evaluation of 356 children obtained and characterized in Projects 1-3: (1) Identify differences in the aberrant profiles specific to different components of reading and to subtypes of reading disabled children. Specifically, we will examine how activation profiles associated with various reading tasks that make different demands on individual component processes may vary for different reading disability subtypes;(2) Establish task-specific features of brain activation profiles associated with response to Tier II instructional remediation, and discern small profile differences contingent on the precise nature and decoding demands of several reading tasks;and (3) Examine task-specific changes of brain activation profiles associated with adequate response to intensive Tier III instruction in children who initially failed to benefit from Tier II intervention in order to assess the degree of normalization vs. compensation in the aberrant profiles of younger and older students after further, more intense intervention. To accomplish these three aims we will make use of recently developed and validated objective and computerized methods for constructing functional brain images on the basis of non-invasive MSI recordings that facilitate disengagement of minute profile differences on averaged and individual subject data. We will also use a range of tasks assessing different components of reading. Altogether, we propose a systematic investigation of different brain profiles that vary with classifications of reading disabilities and in relation to intervention that is closely linked with the other projects in this Center application.